Evaluation of the long-term treatment effects of intravenous idursulfase in patients with mucopolysaccharidosis II (MPS II) using statistical modeling: data from the Hunter Outcome Survey (HOS)

• Published in: Orphanet journal of rare diseases 2021-10, Vol.16 (1), p.456-14, Article 456
• Main Authors: Muenzer, Joseph, Botha, Jaco, Harmatz, Paul, Giugliani, Roberto, Kampmann, Christoph, Burton, Barbara K
• Format: Article
• Language: English
• Subjects: Age; Age groups; Child; Clinical trials; Cognitive ability; Disease; Disease registry; Enrollments; Enzyme Replacement Therapy; Enzymes; Expected values; Genetic disorders; Glycosaminoglycans; Heart; Humans; Hunter syndrome; Iduronate Sulfatase - therapeutic use; Infant; Intravenous administration; Laboratories; Liver; Lysosomal storage disease; Lysosomal storage diseases; Male; Mathematical models; Medical research; Metabolic disorders; MPS II; Mucopolysaccharidosis; Mucopolysaccharidosis II; Mucopolysaccharidosis II - drug therapy; Patients; Rare diseases; Rare Diseases - drug therapy; Statistical modeling; Treatment Outcome; Trends; Ventricle
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-021-02052-4

Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-term treatment outcomes. Using data from patients with MPS II enrolled in the Hunter Outcome Survey (HOS), mixed modeling was performed to evaluate and predict the effects of IV idursulfase treatment on selected clinical parameters for up to 8 years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5 years and who had data available for two or more time points (at least one post-ERT). Age at ERT start and time since ERT start were included as covariates. In total, 481 patients were eligible for inclusion in at least one model. At 8 years post-ERT start, improvement from baseline was predicted for each age group ( 2 cm). Improvements in mean 6-min walk test distance (increase of > 50 m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1 s (decreases of ~ 4 and ~ 9 percentage points, respectively) at 8 years post-ERT start were predicted for patients aged ≥ 5 years at ERT start (these assessments are unsuitable for patients aged